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PLoS Genet. 2010 Dec 16;6(12):e1001249. doi: 10.1371/journal.pgen.1001249.

Functional comparison of innate immune signaling pathways in primates.

Author information

1
Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America. lbarreir@bsd.uchicago.edu

Abstract

Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

PMID:
21187902
PMCID:
PMC3002988
DOI:
10.1371/journal.pgen.1001249
[Indexed for MEDLINE]
Free PMC Article
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